Analysis module 2: Maternal antibodies, study arm, and inflammatory markers by country and ORV response RoVI study — 05 November, 2020

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Methods

Shedding by country/arm

Immunogenicity by country/arm

Any response by country/arm

RV-IgA vs cumulative shedding

Maternal Abs by country/arm/exposure

Maternal Abs vs ORV outcome

EED biomarkers by country/arm/exposure

EED biomarkers vs ORV outcome

Neonatal exposure vs ORV outcome

Methods

Comparisons by country/arm

  • For binary covariates (seroconversion, shedding, etc), comparisons are pairwise Fisher’s exact tests with FDR adjustment.
  • For continuous covariates (titre, inflammatory markers, etc), comparisons are ANOVAs of log-transformed values with post-hoc Tukey tests.
  • * p <0.05; ** p <0.005; *** p <0.0005.

Comparisons by ORV outcome

  • For binary endpoints (seroconversion/shedding), comparisons are logistic regressions.
  • For continuous endpoint (post-vaccination RV-IgA), comparisons are linear regressions of log-transformed RV-IgA concentration.
  • See Module 5 for full univariate and multivariate analyses of ORV outcome.
  • * p <0.05; ** p <0.005; *** p <0.0005.

Shedding by country/arm

Column

Country

Summary of sample sizes

         n neonatal_shedding dose1_shedding dose2_shedding either_shedding
India  307               306            305            306             304
Malawi 119               102            101             83              72
UK      60                58             60             56              56
       seroconv any_response
India       305          302
Malawi      103           61
UK           51           48

ORV shedding

Neonatal and vaccine shedding

Raw data and p values

Neonatal shedding
  proportions positive   n percent
1       India      136 306    44.4
2      Malawi        6 102     5.9
3          UK        1  58     1.7
         p_values      p
1 India vs Malawi 0.0000
2     India vs UK 0.0000
3    Malawi vs UK 0.4235
Dose 1 shedding
  proportions positive   n percent
1       India       82 305    26.9
2      Malawi       56 101    55.4
3          UK       55  60    91.7
         p_values      p
1 India vs Malawi 0.0000
2     India vs UK 0.0000
3    Malawi vs UK 0.0000
Dose 2 shedding
  proportions positive   n percent
1       India       91 306    29.7
2      Malawi       33  83    39.8
3          UK       35  56    62.5
         p_values      p
1 India vs Malawi 0.0860
2     India vs UK 0.0000
3    Malawi vs UK 0.0148
Shedding after either dose
  proportions positive   n percent
1       India      151 304    49.7
2      Malawi       50  72    69.4
3          UK       54  56    96.4
         p_values      p
1 India vs Malawi 0.0025
2     India vs UK 0.0000
3    Malawi vs UK 0.0001
Shedding after both doses
  proportions positive   n percent
1       India       22 304     7.2
2      Malawi       15  72    20.8
3          UK       32  56    57.1
         p_values      p
1 India vs Malawi 0.0015
2     India vs UK 0.0000
3    Malawi vs UK 0.0001
Rota shedding (VP6) by time-point

Raw data and p values

Maternal (MS1)
  proportions positive   n percent
1       India        2 307     0.7
2      Malawi        1  96     1.0
3          UK        2  58     3.4
         p_values      p
1 India vs Malawi 0.5590
2     India vs UK 0.3610
3    Malawi vs UK 0.5590
Week 1 (BS1)
  proportions positive   n percent
1       India      136 306    44.4
2      Malawi        6 102     5.9
3          UK        1  58     1.7
         p_values      p
1 India vs Malawi 0.0000
2     India vs UK 0.0000
3    Malawi vs UK 0.4235
Week 4 (BS2)
  proportions positive   n percent
1       India        0 305     0.0
2      Malawi        3  91     3.3
3          UK        4  57     7.0
         p_values      p
1 India vs Malawi 0.0177
2     India vs UK 0.0017
3    Malawi vs UK 0.4296
Week 6/8 (BS3)
  proportions positive   n percent
1       India        2 305     0.7
2      Malawi        5  88     5.7
3          UK       10  51    19.6
         p_values      p
1 India vs Malawi 0.0110
2     India vs UK 0.0000
3    Malawi vs UK 0.0203
Week 7/9 (BS4)
  proportions positive   n percent
1       India       43 307    14.0
2      Malawi       36  80    45.0
3          UK       49  59    83.1
         p_values      p
1 India vs Malawi 0.0000
2     India vs UK 0.0000
3    Malawi vs UK 0.0000
Week 10/12 (BS5)
  proportions positive   n percent
1       India        8 304     2.6
2      Malawi        9  79    11.4
3          UK       24  54    44.4
         p_values      p
1 India vs Malawi 0.0026
2     India vs UK 0.0000
3    Malawi vs UK 0.0000
Week 11/13 (BS6)
  proportions positive   n percent
1       India       37 306    12.1
2      Malawi       18  84    21.4
3          UK       29  55    52.7
         p_values      p
1 India vs Malawi 0.0345
2     India vs UK 0.0000
3    Malawi vs UK 0.0003
Number of infants with birth shedding, dose 1 shedding, dose 2 shedding and post-vaccination IgA

 India Malawi     UK 
   301     53     50 

Minimum NSP2 Ct among ORV shedders

P values (pairwise Wilcoxon tests with FDR correction)

          comp            p          fdr
1 India-Malawi 4.995433e-03 7.493149e-03
2    UK-Malawi 2.664895e-01 2.664895e-01
3     India-UK 4.574514e-06 1.372354e-05

Arm

Summary of sample sizes

              n neonatal_shedding dose1_shedding dose2_shedding either_shedding
India (IPV) 100                99             99             99              98
India (OPV) 207               207            206            207             206
            seroconv any_response
India (IPV)       99           97
India (OPV)      206          205
Neonatal and vaccine shedding

Raw data and p values

Neonatal shedding
  proportions positive   n percent
1 India (IPV)       37  99    37.4
2 India (OPV)       99 207    47.8
                    p_values      p
1 India (IPV) vs India (OPV) 0.1097
Dose 1 shedding
  proportions positive   n percent
1 India (IPV)       43  99    43.4
2 India (OPV)       39 206    18.9
                    p_values      p
1 India (IPV) vs India (OPV) 0.0000
Dose 2 shedding
  proportions positive   n percent
1 India (IPV)       22  99    22.2
2 India (OPV)       69 207    33.3
                    p_values      p
1 India (IPV) vs India (OPV) 0.0609
Shedding after either dose
  proportions positive   n percent
1 India (IPV)       54  98    55.1
2 India (OPV)       97 206    47.1
                    p_values      p
1 India (IPV) vs India (OPV) 0.2201
Shedding after both doses
  proportions positive   n percent
1 India (IPV)       11  98    11.2
2 India (OPV)       11 206     5.3
                    p_values      p
1 India (IPV) vs India (OPV) 0.0947
Rota shedding (VP6) by time-point

Raw data and p values

Maternal (MS1)
  proportions positive   n percent
1 India (IPV)        1 100     1.0
2 India (OPV)        1 207     0.5
                    p_values      p
1 India (IPV) vs India (OPV) 0.5461
Week 1 (BS1)
  proportions positive   n percent
1 India (IPV)       37  99    37.4
2 India (OPV)       99 207    47.8
                    p_values      p
1 India (IPV) vs India (OPV) 0.1097
Week 4 (BS2)

Not applicable - no shedding observed in IPV arm or OPV arm in week-4 samples.

Week 6/8 (BS3)
  proportions positive   n percent
1 India (IPV)        0 100       0
2 India (OPV)        2 205       1
                    p_values      p
1 India (IPV) vs India (OPV) 1.0000
Week 7/9 (BS4)
  proportions positive   n percent
1 India (IPV)       23 100    23.0
2 India (OPV)       20 207     9.7
                    p_values      p
1 India (IPV) vs India (OPV) 0.0026
Week 10/12 (BS5)
  proportions positive   n percent
1 India (IPV)        6  99     6.1
2 India (OPV)        2 205     1.0
                    p_values      p
1 India (IPV) vs India (OPV) 0.0162
Week 11/13 (BS6)
  proportions positive   n percent
1 India (IPV)        6  99     6.1
2 India (OPV)       31 207    15.0
                    p_values      p
1 India (IPV) vs India (OPV) 0.0251
Number of infants with birth shedding, dose 1 shedding, dose 2 shedding and post-vaccination IgA

India (IPV) India (OPV) 
         96         205 

Minimum NSP2 Ct among ORV shedders

P values

Pairwise Wilcoxon test
     comp         p
1 OPV-IPV 0.4338797

Immunogenicity by country/arm

Column

Country

ORV immunogenicity

Raw data and p values

Seroconversion
  proportions positive   n percent
1       India       85 305    27.9
2      Malawi       24 103    23.3
3          UK       27  51    52.9
         p_values      p
1 India vs Malawi 0.4398
2     India vs UK 0.0009
3    Malawi vs UK 0.0009
Seropositivity, pre-ORV
  proportions positive   n percent
1       India       99 305    32.5
2      Malawi        5 103     4.9
3          UK        2  56     3.6
         p_values      p
1 India vs Malawi 0.0000
2     India vs UK 0.0000
3    Malawi vs UK 1.0000
Seropositivity, post-ORV
  proportions positive   n percent
1       India      154 305    50.5
2      Malawi       26 103    25.2
3          UK       30  54    55.6
         p_values      p
1 India vs Malawi 0.0000
2     India vs UK 0.5556
3    Malawi vs UK 0.0003
Infant RV-IgA pre-vaccination
    gmts   n mean lwr.ci upr.ci
1  India 305    8      6      9
2 Malawi 103    3      3      4
3     UK  56    3      2      4
         p_values      p
1 India vs Malawi 0.0000
2     India vs UK 0.0001
3    Malawi vs UK 0.7334
Infant RV-IgA post-vaccination
    gmts   n mean lwr.ci upr.ci
1  India 305   20     16     25
2 Malawi 103    9      6     12
3     UK  54   27     17     45
         p_values      p
1 India vs Malawi 0.0009
2     India vs UK 0.4886
3    Malawi vs UK 0.0016
Seropositivity by neonatal infection status in India
   
      0   1
  0 138  31
  1  67  68

Pre-vaccination exposure by country (either seropositivity or week-1 shedding)

   
    India Malawi  UK
  0   138     80  52
  1   166     10   2

Arm

ORV immunogenicity

Raw data and p values

Seroconversion
  proportions positive   n percent
1 India (IPV)       25  99    25.3
2 India (OPV)       60 206    29.1
                    p_values      p
1 India (IPV) vs India (OPV) 0.4990
Seropositivity, pre-ORV
  proportions positive   n percent
1 India (IPV)       27  99    27.3
2 India (OPV)       72 206    35.0
                    p_values      p
1 India (IPV) vs India (OPV) 0.1937
Seropositivity, post-ORV
  proportions positive   n percent
1 India (IPV)       47  99    47.5
2 India (OPV)      107 206    51.9
                    p_values      p
1 India (IPV) vs India (OPV) 0.5410
Infant RV-IgA pre-vaccination
         gmts   n mean lwr.ci upr.ci
1 India (IPV)  99    6      4      9
2 India (OPV) 206    8      6     11
                    p_values      p
1 India (IPV) vs India (OPV) 0.1503
Infant RV-IgA post-vaccination
         gmts   n mean lwr.ci upr.ci
1 India (IPV)  99   17     11     25
2 India (OPV) 206   21     16     28
                    p_values      p
1 India (IPV) vs India (OPV) 0.3423

Any response by country/arm

Column

Country

Any response

Raw data and p values

  proportions positive   n percent
1       India      181 302    59.9
2      Malawi       43  61    70.5
3          UK       46  48    95.8
         p_values      p
1 India vs Malawi 0.1487
2     India vs UK 0.0000
3    Malawi vs UK 0.0012

Arm

Any response

Raw data and p values

  proportions positive   n percent
1 India (IPV)       62  97    63.9
2 India (OPV)      119 205    58.0
                    p_values      p
1 India (IPV) vs India (OPV) 0.3792

RV-IgA vs cumulative shedding

Column

Number of infants with birth shedding, dose 1 shedding, dose 2 shedding, pre-vaccination IgA and post-vaccination IgA

 India Malawi     UK 
   301     53     47 

Cumulative effect of birth exposure and vaccination on IgA titre

Exposure defined as week-1 shedding or IgA positivity pre-vaccination. Shedding subgroups with <5 infants excluded.
        
         -- -+ +- ++
  India  53 84 99 65
  Malawi 16 33  2  2
  UK      2 44  0  1

P values

India
$`s1I$shedding_group`
           diff         lwr       upr        p adj
-+--- 0.2517953 -0.07304050 0.5766310 1.892829e-01
+---- 0.9803076  0.66513578 1.2954794 1.041944e-12
++--- 1.3756276  1.03291698 1.7183382 9.058310e-13
+---+ 0.7285123  0.45381817 1.0032065 2.530073e-10
++--+ 1.1238323  0.81793338 1.4297312 9.047207e-13
++-+- 0.3953200  0.09970339 0.6909365 3.510221e-03
Malawi
$`s1M$shedding_group`
           diff       lwr       upr       p adj
-+--- 0.4989606 0.1278144 0.8701068 0.009495288

Maternal Abs by country/arm/exposure

Column

Country

Number of Indian infants with MB IgA, MB IgG, CB IgG, BB1 IgG and no pre-vaccination RV exposure

[1] 138

Pearson’s correlation coefficient for MB RV-IgA and MB RV-IgG (log transformed)


    Pearson's product-moment correlation

data:  log(t$MB1_IgA) and log(t$MB1_IgG)
t = 8.254, df = 136, p-value = 1.185e-13
alternative hypothesis: true correlation is not equal to 0
95 percent confidence interval:
 0.4544851 0.6792457
sample estimates:
      cor 
0.5777145 

Maternal IgA antibody levels

Raw data and p values

Maternal RV-IgA
    gmts   n mean lwr.ci upr.ci
1  India 305  134    120    150
2 Malawi 103  340    256    452
3     UK  49  186    123    281
         p_values      p
1 India vs Malawi 0.0000
2     India vs UK 0.1649
3    Malawi vs UK 0.0089
Breastmilk RV-IgA
    gmts   n mean lwr.ci upr.ci
1  India 301   25     22     29
2 Malawi  78   97     84    112
3     UK  30  100     68    146
         p_values      p
1 India vs Malawi 0.0000
2     India vs UK 0.0000
3    Malawi vs UK 0.9932

Arm

Antibody levels

Raw data and p values

Maternal RV-IgA
         gmts   n mean lwr.ci upr.ci
1 India (IPV)  99  151    123    186
2 India (OPV) 206  126    110    145
                    p_values      p
1 India (IPV) vs India (OPV) 0.1456
Breastmilk RV-IgA
         gmts   n mean lwr.ci upr.ci
1 India (IPV)  99   26     20     33
2 India (OPV) 202   25     21     30
                    p_values      p
1 India (IPV) vs India (OPV) 0.8516
Maternal RV-IgG
         gmts   n  mean lwr.ci upr.ci
1 India (IPV)  99 11150   9185  13536
2 India (OPV) 206  9539   8318  10938
                    p_values      p
1 India (IPV) vs India (OPV) 0.1978
Cord-blood RV-IgG
         gmts   n  mean lwr.ci upr.ci
1 India (IPV)  99 15482  12986  18456
2 India (OPV) 206 13190  11436  15212
                    p_values      p
1 India (IPV) vs India (OPV) 0.1869

Exposure status

Antibody levels

Raw data and p values

Maternal RV-IgA
               gmts   n mean lwr.ci upr.ci
1   India (exposed) 166  131    113    152
2 India (unexposed) 138  138    115    165
                              p_values      p
1 India (exposed) vs India (unexposed) 0.6633
Breastmilk RV-IgA
               gmts   n mean lwr.ci upr.ci
1   India (exposed) 163   24     20     28
2 India (unexposed) 137   28     22     34
                              p_values      p
1 India (exposed) vs India (unexposed) 0.2795
Maternal RV-IgG
               gmts   n  mean lwr.ci upr.ci
1   India (exposed) 166  9642   8305  11195
2 India (unexposed) 138 10476   8835  12422
                              p_values      p
1 India (exposed) vs India (unexposed) 0.4684
Cord-blood RV-IgG
               gmts   n  mean lwr.ci upr.ci
1   India (exposed) 166 13497  11761  15489
2 India (unexposed) 138 14279  11873  17171
                              p_values      p
1 India (exposed) vs India (unexposed) 0.6230

Maternal Abs vs ORV outcome

Column

Summary

See Module 5 for full univariate and multivariate analyses.

Correlation networks

India

Correlation between of MB1 IgA and CB IgG


    Pearson's product-moment correlation

data:  log(s_sub$MB1_IgA) and log(s_sub$CB1_IgG)
t = 7.8633, df = 303, p-value = 6.625e-14
alternative hypothesis: true correlation is not equal to 0
95 percent confidence interval:
 0.3138832 0.5008302
sample estimates:
      cor 
0.4116784 

Full correlation network

Number with complete antibody data = 297

India (exposed subset)

Number with complete antibody data = 161

India (unexposed subset)

Number with complete antibody data = 136

Malawi

Full correlation network

Number with complete antibody data = 42

UK

Full correlation network

Number with complete antibody data = 40 (breastmilk IgA data excluded as this reduced the number of complete cases from 40 to 22).

Continuous outcomes

Pearson correlation coefficients: maternal antibodies vs pre-vaccination RV-IgA

Pearson correlation coefficients
           India_exposed
MB1 RV-IgA       -0.1500
BM1 RV-IgA       -0.1191
MB1 RV-IgG       -0.4216
CB1 RV-IgG       -0.3843
BB1 RV-IgG        0.2170
P values
           India_exposed
MB1 RV-IgA        0.0537
BM1 RV-IgA        0.1298
MB1 RV-IgG        0.0000
CB1 RV-IgG        0.0000
BB1 RV-IgG        0.0050

Pearson correlation coefficients: maternal antibodies vs post-vaccination RV-IgA

Pearson correlation coefficients
             India India_exposed India_unexposed  Malawi      UK
MB1 RV-IgA -0.1298       -0.1816         -0.0930 -0.2884 -0.1168
BM1 RV-IgA -0.1367       -0.1077         -0.1599 -0.2594  0.1924
MB1 RV-IgG -0.2608       -0.3711         -0.1644      NA      NA
CB1 RV-IgG -0.2109       -0.3291         -0.1209      NA      NA
BB1 RV-IgG  0.1027        0.0136         -0.1134      NA      NA
P values
            India India_exposed India_unexposed Malawi     UK
MB1 RV-IgA 0.0234        0.0192          0.2782 0.0031 0.4446
BM1 RV-IgA 0.0176        0.1710          0.0619 0.0218 0.3175
MB1 RV-IgG 0.0000        0.0000          0.0540     NA     NA
CB1 RV-IgG 0.0002        0.0000          0.1579     NA     NA
BB1 RV-IgG 0.0734        0.8617          0.1856     NA     NA

Effect modification

Model for final RV-IgA vs MB RV-IgA + country


Call:
lm(formula = log(BB2_IgA) ~ log(MB1_IgA) + country, data = s)

Residuals:
    Min      1Q  Median      3Q     Max 
-3.9242 -1.5926 -0.0985  1.4952  5.3765 

Coefficients:
              Estimate Std. Error t value Pr(>|t|)    
(Intercept)    4.32175    0.39380  10.975  < 2e-16 ***
log(MB1_IgA)  -0.27278    0.07719  -3.534 0.000452 ***
countryMalawi -0.55130    0.23086  -2.388 0.017352 *  
countryUK      0.43999    0.30847   1.426 0.154453    
---
Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1

Residual standard error: 1.925 on 449 degrees of freedom
  (33 observations deleted due to missingness)
Multiple R-squared:  0.06128,   Adjusted R-squared:  0.05501 
F-statistic: 9.771 on 3 and 449 DF,  p-value: 2.956e-06

Model with interaction terms


Call:
lm(formula = log(BB2_IgA) ~ log(MB1_IgA) * factor(country), data = s)

Residuals:
    Min      1Q  Median      3Q     Max 
-3.8672 -1.5512 -0.1094  1.4675  5.3505 

Coefficients:
                                   Estimate Std. Error t value Pr(>|t|)    
(Intercept)                         4.25958    0.54646   7.795 4.57e-14 ***
log(MB1_IgA)                       -0.26009    0.10927  -2.380   0.0177 *  
factor(country)Malawi              -0.04537    0.96101  -0.047   0.9624    
factor(country)UK                  -0.16984    1.19857  -0.142   0.8874    
log(MB1_IgA):factor(country)Malawi -0.08881    0.17107  -0.519   0.6039    
log(MB1_IgA):factor(country)UK      0.11579    0.22476   0.515   0.6067    
---
Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1

Residual standard error: 1.928 on 447 degrees of freedom
  (33 observations deleted due to missingness)
Multiple R-squared:  0.06291,   Adjusted R-squared:  0.05243 
F-statistic: 6.001 on 5 and 447 DF,  p-value: 2.177e-05

Comparison of fit

Analysis of Variance Table

Model 1: log(BB2_IgA) ~ log(MB1_IgA) + country
Model 2: log(BB2_IgA) ~ log(MB1_IgA) * factor(country)
  Res.Df    RSS Df Sum of Sq      F Pr(>F)
1    449 1663.8                           
2    447 1660.9  2    2.8825 0.3879 0.6787

India vs Malawi

Analysis of Variance Table

Model 1: log(BB2_IgA) ~ log(MB1_IgA) + factor(country)
Model 2: log(BB2_IgA) ~ log(MB1_IgA) * factor(country)
  Res.Df  RSS Df Sum of Sq      F Pr(>F)
1    405 1517                           
2    404 1516  1    1.0014 0.2669 0.6057

UK vs India/Malawi

Analysis of Variance Table

Model 1: log(BB2_IgA) ~ log(MB1_IgA) + factor(country == "UK")
Model 2: log(BB2_IgA) ~ log(MB1_IgA) * factor(country == "UK")
  Res.Df    RSS Df Sum of Sq      F Pr(>F)
1    450 1684.9                           
2    449 1681.0  1    3.8696 1.0336 0.3099

Exposure status (within in India)

Analysis of Variance Table

Model 1: log(BB2_IgA) ~ log(MB1_IgA) + factor(pre_exposed)
Model 2: log(BB2_IgA) ~ log(MB1_IgA) * factor(pre_exposed)
  Res.Df    RSS Df Sum of Sq      F Pr(>F)
1    301 846.95                           
2    300 843.40  1    3.5517 1.2633 0.2619

No significant evidence that the association between maternal RV-IgA and infant post-vaccination RV-IgA differs by country or between high-income settings (UK) vs LMICs (India/Malawi).

EED biomarkers by country/arm/exposure

Column

Country

EED biomarker levels

Raw data and p values

α1AT (week 6/8)
    gmts   n mean lwr.ci upr.ci
1  India 301  734    676    796
2 Malawi  83 4376   3136   6105
3     UK  48  282    155    511
         p_values      p
1 India vs Malawi 0.0000
2     India vs UK 0.0000
3    Malawi vs UK 0.0000
MPO (week 6/8)
    gmts   n mean lwr.ci upr.ci
1  India 301 6463   5446   7672
2 Malawi  83 2966   2454   3585
3     UK  47 3766   2413   5878
         p_values      p
1 India vs Malawi 0.0000
2     India vs UK 0.0399
3    Malawi vs UK 0.6234
α1AG (week 6)
    gmts   n  mean lwr.ci upr.ci
1  India 304 722.8  702.8  743.5
2 Malawi  87   519  454.1  593.3
$`t$country`
                   diff        lwr        upr p adj
Malawi-India -0.3312002 -0.4191556 -0.2432447     0
α1AT (week 10/12)
    gmts   n  mean lwr.ci upr.ci
1  India 298   820    742    906
2 Malawi  63  9222   6642  12803
3     UK  51   508    338    763
         p_values      p
1 India vs Malawi 0.0000
2     India vs UK 0.0065
3    Malawi vs UK 0.0000
MPO (week 10/12)
    gmts   n mean lwr.ci upr.ci
1  India 298 7327   6193   8669
2 Malawi  63 4135   3098   5518
3     UK  51 3082   1974   4812
         p_values      p
1 India vs Malawi 0.0124
2     India vs UK 0.0003
3    Malawi vs UK 0.5271

Arm

EED biomarker levels

Raw data and p values

α1AT (week 6)
         gmts   n mean lwr.ci upr.ci
1 India (IPV)  97  759    650    887
2 India (OPV) 202  719    653    793
                    p_values      p
1 India (IPV) vs India (OPV) 0.5486
MPO (week 6)
         gmts   n mean lwr.ci upr.ci
1 India (IPV)  97 5291   3902   7176
2 India (OPV) 202 7041   5712   8678
                    p_values      p
1 India (IPV) vs India (OPV) 0.1264
α1AG (week 6)
         gmts   n mean lwr.ci upr.ci
1 India (IPV)  98  708    673    745
2 India (OPV) 205  730    705    755
                    p_values      p
1 India (IPV) vs India (OPV) 0.3207
α1AT (week 10)
         gmts   n mean lwr.ci upr.ci
1 India (IPV)  96  794    673    937
2 India (OPV) 200  829    731    940
                    p_values      p
1 India (IPV) vs India (OPV) 0.6920
MPO (week 10)
         gmts   n mean lwr.ci upr.ci
1 India (IPV)  96 7072   5320   9403
2 India (OPV) 200 7598   6161   9371
                    p_values      p
1 India (IPV) vs India (OPV) 0.6954

Exposure status

EED biomarker levels

Raw data and p values

α1AT (week 6)
               gmts   n mean lwr.ci upr.ci
1   India (exposed) 163  714    639    797
2 India (unexposed) 136  755    666    856
                              p_values      p
1 India (exposed) vs India (unexposed) 0.5020
MPO (week 6)
               gmts   n mean lwr.ci upr.ci
1   India (exposed) 163 6365   5043   8033
2 India (unexposed) 136 6481   5004   8396
                              p_values      p
1 India (exposed) vs India (unexposed) 0.9177
α1AG (week 6)
               gmts   n mean lwr.ci upr.ci
1   India (exposed) 165  714    687    742
2 India (unexposed) 138  733    703    765
                              p_values      p
1 India (exposed) vs India (unexposed) 0.3524
α1AT (week 10)
               gmts   n mean lwr.ci upr.ci
1   India (exposed) 162  771    667    891
2 India (unexposed) 134  878    766   1006
                              p_values      p
1 India (exposed) vs India (unexposed) 0.2020
MPO (week 10/12)
               gmts   n  mean lwr.ci upr.ci
1   India (exposed) 162  6611   5234   8350
2 India (unexposed) 134  8540   6699  10888
                              p_values      p
1 India (exposed) vs India (unexposed) 0.1361

EED biomarkers vs ORV outcome

Summary

See Module 5 for full univariate and multivariate analyses.

Continuous outcomes

Pearson correlation coefficients: EED markers vs pre-vaccination RV-IgA

Pearson correlation coefficients
               India_exposed
α1AT (week 6)         0.0581
α1AT (week 10)       -0.0204
MPO (week 6)          0.1368
MPO (week 10)         0.0387
α1AG (week 6)         0.0306
P values
               India_exposed
α1AT (week 6)         0.0192
α1AT (week 10)        0.1710
MPO (week 6)          0.0000
MPO (week 10)         0.0000
α1AG (week 6)         0.8617

Pearson correlation coefficients: EED vs post-vaccination RV-IgA

Pearson correlation coefficients
                    India India_exposed India_unexposed  Malawi      UK
α1AT (week 6/8)   -0.0325        0.0597         -0.0996 -0.0601 -0.0815
α1AT (week 10/12) -0.0624       -0.0298         -0.0102  0.0835  0.2202
MPO (week 6/8)    -0.0294        0.0343         -0.1183 -0.0318 -0.0388
MPO (week 10/12)  -0.1112       -0.0618         -0.1239  0.0242 -0.2363
α1AG (week 6)     -0.0818       -0.1074          0.0041 -0.0230      NA
P values
                   India India_exposed India_unexposed Malawi     UK
α1AT (week 6/8)   0.5748        0.4489          0.2485 0.6013 0.6036
α1AT (week 10/12) 0.2836        0.7064          0.9069 0.5521 0.1325
MPO (week 6/8)    0.6125        0.6641          0.1702 0.7824 0.8072
MPO (week 10/12)  0.0556        0.4347          0.1538 0.8637 0.1138
α1AG (week 6)     0.1546        0.1699          0.9617 0.8327     NA

Neonatal exposure vs ORV outcome

Column

Pre-exposure by cohort

   
    India Malawi  UK
  0   138     80  52
  1   166     10   2

Pre-exposure defined as detection of week-1 shedding (VP6 Ct <35) or seropositivity pre-vaccination (RV-IgA ≥20 IU/ml)

ORV response by exposure status (with Malawi and UK as comparison groups)

Raw data and p values

Dose 1 shedding
        proportions positive   n percent     p
1   India (exposed)       29 164    17.7 1e-04
2 India (unexposed)       52 138    37.7    NA
Shedding of either dose
        proportions positive   n percent     p
1   India (exposed)       65 164    39.6 2e-04
2 India (unexposed)       84 137    61.3    NA
Seroconversion
        proportions positive   n percent      p
1   India (exposed)       51 166    30.7 0.2508
2 India (unexposed)       34 138    24.6     NA
Pre-ORV RV-IgA
              group mean lwr.ci upr.ci  p
1 India (unexposed)  1.9    1.7    2.2  0
2   India (exposed) 23.7   18.1   31.1 NA
Post-ORV RV-IgA
              group mean lwr.ci upr.ci  p
1 India (unexposed)  5.9    4.6    7.6  0
2   India (exposed) 55.1   41.8   72.8 NA
Any response
        proportions positive   n percent      p
1   India (exposed)       87 164    53.0 0.0096
2 India (unexposed)       93 137    67.9     NA